Genetic Variant NM_003621.5:c.888+63C>G (chr11-7628409-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003621.5(PPFIBP2):c.888+63C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.463 in 1,457,538 control chromosomes in the GnomAD database, including 158,911 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20732 hom., cov: 32)

Exomes 𝑓: 0.46 ( 138179 hom. )

Consequence

PPFIBP2
NM_003621.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.352

Publications

8 publications found

Variant links:

Genes affected

PPFIBP2 (HGNC:9250): (PPFIA binding protein 2) This gene encodes a member of the LAR protein-tyrosine phosphatase-interacting protein (liprin) family. The encoded protein is a beta liprin and plays a role in axon guidance and neuronal synapse development by recruiting LAR protein-tyrosine phosphatases to the plasma membrane. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]

PPFIBP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPFIBP2	NM_003621.5 link	c.888+63C>G		intron_variant	Intron 9 of 23	ENST00000299492.9	NP_003612.3	Q8ND30-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPFIBP2	ENST00000299492.9 link	c.888+63C>G		intron_variant	Intron 9 of 23	1	NM_003621.5	ENSP00000299492.4		Q8ND30-1

Frequencies

GnomAD3 genomes

AF:

0.512

AC:

77780

AN:

151898

Hom.:

20712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.670

Gnomad AMI

AF:

0.549

Gnomad AMR

AF:

0.441

Gnomad ASJ

AF:

0.481

Gnomad EAS

AF:

0.619

Gnomad SAS

AF:

0.349

Gnomad FIN

AF:

0.411

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.517

GnomAD4 exome

AF:

0.457

AC:

596937

AN:

1305522

Hom.:

138179

AF XY:

0.454

AC XY:

298368

AN XY:

657188

show subpopulations

African (AFR)

AF:

0.686

AC:

20695

AN:

30164

American (AMR)

AF:

0.386

AC:

16588

AN:

43020

Ashkenazi Jewish (ASJ)

AF:

0.486

AC:

12041

AN:

24784

East Asian (EAS)

AF:

0.631

AC:

24477

AN:

38798

South Asian (SAS)

AF:

0.357

AC:

28982

AN:

81072

European-Finnish (FIN)

AF:

0.416

AC:

22086

AN:

53066

Middle Eastern (MID)

AF:

0.510

AC:

2781

AN:

5450

European-Non Finnish (NFE)

AF:

0.455

AC:

443235

AN:

973936

Other (OTH)

AF:

0.472

AC:

26052

AN:

55232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

15547

31094

46640

62187

77734

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12726

25452

38178

50904

63630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.512

AC:

77841

AN:

152016

Hom.:

20732

Cov.:

AF XY:

0.507

AC XY:

37649

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.670

AC:

27740

AN:

41426

American (AMR)

AF:

0.441

AC:

6735

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.481

AC:

1668

AN:

3470

East Asian (EAS)

AF:

0.619

AC:

3194

AN:

5162

South Asian (SAS)

AF:

0.348

AC:

1678

AN:

4824

European-Finnish (FIN)

AF:

0.411

AC:

4347

AN:

10572

Middle Eastern (MID)

AF:

0.497

AC:

145

AN:

292

European-Non Finnish (NFE)

AF:

0.452

AC:

30749

AN:

67964

Other (OTH)

AF:

0.514

AC:

1084

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1896

3792

5688

7584

9480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.307

Hom.:

687

Bravo

AF:

0.527

Asia WGS

AF:

0.461

AC:

1603

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Benign

0.85

PhyloP100

0.35

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over